The proposal is a longitudinal study of potential neurobiological and neurobehavioral markers of disease onset and progression in pre-symptomatic individuals who have the CAG expansion in the HD gene. A total of 500 subjects will be enrolled. Study subjects will be 30 to 55 years old and have a parental history of Huntington's disease. The study will enroll 425 cases with >39 CAG repeats (affected), and 75 controls with <30 CAG repeats (wildtype). The patients will be recruited from 20 research sites in the United States and Canada. Subjects will be evaluated every 12 months for up to 5 years. At baseline, blood will be drawn for centralized confirmatory gene testing. At every visit, subjects will undergo standardized assessments of motor, cognitive, functional, and psychiatric signs of HD using the Unified Huntington's Disease Rating Scale (UHDRS). More comprehensive evaluations will be done at baseline, and 24 and 48 months of follow-up. These more comprehensive evaluations will include a videotaped examination, volumetric magnetic resonance imaging, detailed neuropsychometric testing and behavioral ratings.